Hard ticks (Acari: Ixodidae) infesting domestic animals in Egypt: diagnostic characters and a taxonomic key to the collected species.

Ticks are important vectors of emerging health problems in humans and animals. We conducted several field surveillances to investigate the fauna of hard ticks on domestic animals in seven governorates of Egypt during 2018-2019. A total of 3265 individual tick specimens were collected and identified to the species level; the specimens belong to 11 species within three genera (Amblyomma, Hyalomma, and Rhipicephalus). Tick infestation was highest in dromedary camels (70%), followed by dogs (52.5%), cattle (50%), buffaloes (38%), and horses (12%). Ten species were collected from dromedary camels, 2 from cattle, and one species from dogs, buffaloes, and horses. Diagnostic characters with high-quality photographic images of the 11 tick species were provided. New measurements of the body regions such as spiracles and body grooves were also obtained to provide further details on morphological variations among the diverse tick species. This study provided detailed descriptions of the genital apertures of five Hyalomma species. Morphological variations of male Hyalomma impeltatum, and genital apertures of female Hyalomma dromedarii and Hyalomma excavatum were also examined in this study. Finally, we provided additional details on local geographic distributions, hosts, endemicity status, and disease relationships of the eleven tick species.

A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis.

OBJECTIVES: Recent genome-wide association studies disclosed that several single nucleotide polymorphisms (SNPs), including tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) (+16860A/G), are associated with the pathophysiology of rheumatoid arthritis (RA). We assessed the usefulness of TRAF1 genotyping as a genetic predictor of the response to anti-TNF treatment in Japanese RA patients. METHODS: TRAF1 (+16860A/G) was genotyped using the TaqMan SNP genotyping assay in 101 Japanese RA patients treated with anti-TNF drugs for >24 weeks. We retrospectively analysed the association between SNP and the clinical response to treatment. TRAF1 mRNA and protein expression was also evaluated in CD4+, CD8+, CD14+, or CD19+ cells from 25 healthy subjects using quantitative polymerase chain reaction and intracellular staining flow cytometry, respectively. RESULTS: No statistical difference in DAS28-ESR at baseline was observed between the patient groups with the AA, AG, or GG genotype. The GG genotype was more frequent in non-responders than in good or moderate responders [odds ratio (OR) 7.4, 95% confidence interval (CI) 1.5-37.5]. The non-responders possessed the G allele more frequently than the good or moderate responders (OR 3.5, 95% CI 1.4-9.0). TRAF1 protein expression increased significantly in CD14+ monocytes from healthy subjects with the GG genotype compared with that in subjects with the AA or AG genotype. CONCLUSIONS: TRAF1 (+16860A/G) may be useful for predicting the clinical response to anti-TNF treatment and may contribute to resistance to treatment in RA patients with the GG genotype by increasing the TRAF1 expression in circulating inflammatory cells.

[Genotype-phenotype correlations in familial hypertrophic cardiomyopathy].

Familial hypertrophic cardiomyopathy(FHC) is a complex cardiac disease with unique pathophysiological characteristics and a great diversity of morphological, functional, and clinical features. The results of molecular genetic studies have shown that FHC is a disease of the sarcomere involving eight different genes encoding proteins of the myofibrillar apparatus. Recent advances in genetic studies have provided insights into the heterogeneity of FHC clinical features. Analyses of genotype-phenotype correlations in FHC have shown that the age-related penetrance, the pattern of the left ventricular hypertrophy, and the prognosis are different depending on the disease causing genes or the disease causing mutations. Understanding of the genotype-phenotype correlations in FHC is useful for management of the disease.

Perceived social support mediates between prior attachment and subsequent adjustment: a study of urban African American children.

The processes whereby attachment and other social and cognitive factors contribute to social and emotional adjustment were examined. Participants were 56 African American children from low-income urban families. Attachment and sociability were assessed in the strange situation when children were 4.5 years old. Two years later, children were interviewed regarding their perceptions of social support and their attributions about others' intentions. Also assessed at Time 2 were child verbal intelligence, defensive response style, children's self-reports, and parent reports of child adjustment. As expected, attachment uniquely predicted perceived social support. Insecure attachment predicted self-reports of behavior problems and parental report of internalizing problems. Perceived social support was associated positively and significantly with viewing ambiguously depicted actions as prosocial rather than aggressive. Perceived social support was found to mediate the relation between attachment and adjustment. Results suggest that behaviorally mediated strategies for relating to caregivers in early childhood predict generalized social perception, thought, and emotion at later ages.

Patients with familial hypertrophic cardiomyopathy caused by a Phe110Ile missense mutation in the cardiac troponin T gene have variable cardiac morphologies and a favorable prognosis.

BACKGROUND: Mutations that cause familial hypertrophic cardiomyopathy have been identified in several genes that encode contractile proteins. Patients with mutations in the cardiac troponin T (cTnT) gene have particularly poor prognosis but only mild hypertrophy. To date, no benign mutation in the cTnT gene has been reported. The clinical characteristics and prognosis of patients with the Phe110Ile mutation in the cTnT gene is unclear because few affected individuals have been identified. METHODS AND RESULTS: Forty-six probands with familial hypertrophic cardiomyopathy were screened for mutations in the cTnT gene. The Phe110Ile missense mutation was found in 6 probands. Individuals in the 6 families were analyzed genetically and clinically. Haplotype analysis was performed with markers encompassing the cTnT gene. Left ventricular hypertrophy was classified as type I, II, III, or IV according to the criteria of Maron et al. The Phe110Ile mutation in the cTnT gene was identified in 16 individuals. Two of the 6 families shared the same flanking haplotype, and 4 were different from each other. Affected individuals exhibited different cardiac morphologies: 4 had type II, 6 had type III, and 3 had type IV hypertrophy with apical involvement. Three individuals with the disease-causing mutation did not fulfill clinical criteria for the disease. The product-limit survival curve analysis demonstrated a favorable prognosis. CONCLUSIONS: Multiple independent mutations of residue 340 in the cTnT gene have been described, suggesting that this may be a "hot spot" for such events. The Phe110Ile substitution causes hypertrophic cardiomyopathy with variable cardiac morphologies and a favorable prognosis.

Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3.

We have mapped a disease locus for Wolff-Parkinson-White syndrome (WPW) and familial hypertrophic cardiomyopathy (FHC) segregating in a large kindred to chromosome 7 band q3. Although WPW syndrome and FHC have been observed in members of the same family in prior studies, the relationship between these two diseases has remained enigmatic. A large family with 25 surviving individuals who are affected by one or both of these conditions was studied. The disease locus is closely linked to loci D7S688, D7S505, and D7S483 (maximum two point LOD score at D7S505 was 7.80 at theta = 0). While four different FHC loci have been described this is the first locus that can be mutated to cause both WPW and/or FHC.

A de novo mutation in alpha-tropomyosin that causes hypertrophic cardiomyopathy.

BACKGROUND: Two missense mutations in the gene for alpha-tropomyosin have been described that segregate with hypertrophic cardiomyopathy in single families. To confirm that these mutations are the cause of the disease, we have investigated the origins of one of these mutations, Asp175Asn, in a third and unrelated family. METHODS AND RESULTS: The presence or absence of an alpha-tropomyosin mutation and the haplotypes of the flanking chromosomal regions were determined for members of a family with hypertrophic cardiomyopathy. Haplotypes were constructed by use of an intragenic polymorphism and 10 flanking polymorphisms spanning a region of 35 centimorgans. The Asp175Asn missense mutation was present in the proband and his two affected offspring but not in any of the proband's three siblings. Although both parents were deceased, the haplotypes of the four parental chromosomes could be reconstructed. One parental chromosome was transmitted to two offspring: one bearing the Asp175Asn mutation (the affected proband) and one clinically unaffected sibling who lacked the alpha-tropomyosin mutation. Thus, the Asp175Asn mutation must have arisen de novo. CONCLUSIONS: De novo mutations in the alpha-tropomyosin gene can result in hypertrophic cardiomyopathy that may appear to be sporadic but in subsequent generations gives rise to familial disease. Individuals with sporadic hypertrophic cardiomyopathy should be advised of the risk of transmission to offspring. In addition, these findings provide the strongest genetic evidence that mutations in the alpha-tropomyosin gene are directly responsible for hypertrophic cardiomyopathy.

Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy can be caused by mutations in the genes for beta cardiac myosin heavy chain, alpha-tropomyosin, or cardiac troponin T. It is not known how often the disease is caused by mutations in the tropomyosin and troponin genes, and the associated clinical phenotypes have not been carefully studied. METHODS: Linkage between polymorphisms of the alpha-tropomyosin gene or the cardiac troponin T gene and hypertrophic cardiomyopathy was assessed in 27 families. In addition, 100 probands were screened for mutations in the alpha-tropomyosin gene, and 26 were screened for mutations in the cardiac troponin T gene. Life expectancy, the incidence of sudden death, and the extent of left ventricular hypertrophy were compared in patients with different mutations. RESULTS: Genetic analyses identified only one alpha-tropomyosin mutation, identical to one previously described. Five novel mutations in cardiac troponin were identified, as well as a further example of a previously described mutation. The clinical phenotype of four troponin T mutations in seven unrelated families was similar and was characterized by a poor prognosis (life expectancy, approximately 35 years) and a high incidence of sudden death. The mean (+/- SD) maximal thickness of the left ventricular wall in subjects with cardiac troponin T mutations (16.7 +/- 5.5 mm) was significantly less than that in subjects with beta cardiac myosin heavy-chain mutations (23.7 +/- 7.7 mm, P < 0.001). CONCLUSIONS: Mutations in alpha-tropomyosin are a rare cause of familial hypertrophic cardiomyopathy, accounting for approximately 3 percent of cases. Mutations in cardiac troponin T account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy in this referral-center population. These mutations are characterized by relatively mild and sometimes subclinical hypertrophy but a high incidence of sudden death. Genetic testing may therefore be especially important in this group.

Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects.

BACKGROUND: Mutations of mitochondrial DNA have been demonstrated as causes of human mitochondrial diseases. While these disorders typically involve multiple organs, the effect of mitochondrial mutations on the heart has not been systematically studied. METHODS AND RESULTS: We studied mitochondrial mutations and cardiac changes in 17 patients with Kearns-Sayre syndrome; ocular myopathy; myoclonus epilepsy with ragged red fibers (MERRF); and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Cardiac involvement was evaluated by chest radiograph, ECG, His-bundle electrogram, and echocardiogram. All 3 patients with Kearns-Sayre syndrome had large deletions of mitochondrial DNA and disturbances in cardiac conduction. ECG abnormalities were found in 2 of 6 patients with ocular myopathy who showed large deletions of mitochondrial DNA. All 3 patients with MERRF had an A-to-G mutation at nucleotide position 8344; 2 had cardiomegaly, asymmetrical septal hypertrophy, and diffuse hypokinesis of the left ventricle. One patient with asymmetrical septal hypertrophy developed dilated cardiomyopathy 2 years later. All 5 patients with MELAS had an A-to-G mutation at nucleotide position 3243, and 2 had symmetrical left ventricular hypertrophy with or without abnormal wall motion. CONCLUSIONS: The clinical features of cardiac involvement in mitochondrial diseases vary in the different subgroups of these disorders. Particular mitochondrial mutations can cause characteristic cardiac abnormalities.

Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy.

Three novel beta cardiac myosin heavy chain (MHC) gene missense mutations, Phe513Cys, Gly716Arg, and Arg719Trp, which cause familial hypertrophic cardiomyopathy (FHC) are described. One mutation in exon 15 (Phe513Cys) does not alter the charge of the encoded amino acid, and affected family members have a near normal life expectancy. The Gly716Arg mutation (exon 19; charge change of +1) causes FHC in three family members, one of whom underwent transplantation for heart failure. The Arg719Trp mutation (exon 19; charge change of -1) was found in four unrelated FHC families with a high incidence of premature death and an average life expectancy in affected individuals of 38 yr. A comparable high frequency of disease-related deaths in four families with the Arg719Trp mutation suggests that this specific gene defect directly accounts for the observed malignant phenotype. Further, the significantly different life expectancies associated with the Arg719Trp vs. Phe513Cys mutation (P < 0.001) support the hypothesis that mutations which alter the charge of the encoded amino acid affect survival more significantly than those that produce a conservative amino acid change.

Independent origin of identical beta cardiac myosin heavy-chain mutations in hypertrophic cardiomyopathy.

The origins of the beta cardiac myosin heavy-chain (MHC) gene missense mutations that cause familial hypertrophic cardiomyopathy (FHC) in 14 families have been evaluated. Of eight different mutations, four were present in single families, while four occurred in two or more families. To investigate the origins of the four shared mutations, we defined the beta cardiac MHC haplotypes of each of the mutation-bearing chromosomes by determining the alleles present at three intragenic polymorphic loci. Two of the mutations (Arg453Cys and Val606Met) have arisen independently in each of three families, being found on different chromosomal backgrounds. A third mutation (Gly584Arg) is associated with identical haplotypes in two families with Portuguese ancestors, suggesting a founder effect. Haplotype analysis was uninformative for the fourth mutation (Arg403Gln). Thus, FHC-causing mutations have arisen independently in at least 12 of the 14 families studied, suggesting that the majority have arisen relatively recently as new mutations. This finding predicts the prevalence of disease-causing beta cardiac MHC mutations to be comparable in all population groups.

Deletion of mitochondrial DNA in the endomyocardial biopsy sample from a patient with Kearns-Sayre syndrome.

A 15-year-old boy with Kearns-Sayre syndrome is reported. The deletion of mitochondrial DNA in the endomyocardial biopsy sample from the patient was confirmed by the polymerase chain reaction method, and was identified to that in the skeletal muscle.

[Clinical study on myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy].

Myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with 201Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of 123I-BMIPP compared to 201Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of 123I-BMIPP was higher than that of 201Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of 123I-BMIPP was lower than that of 201Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of 125I-BMIPP, these results suggest that 123I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy.

[Cardiac involvement in mitochondrial disease: a clinical study of 38 patients].

Several reports showed that abnormality of mitochondrial DNA (mt DNA) can be an etiology of cardiomyopathy in recent years. Cardiac involvement in mitochondrial disease other than Kearns-Sayre syndrome (KSS), however, has not been documented clearly. Therefore, cardiac involvement, abnormality of mt DNA and defects of the respiratory chain in mitochondrial disease were studied. Thirty-eight patients with mitochondrial disease were studied. The patients were consisted of 2 patients with KSS, 1 patient with probable KSS, 15 patients with ocular myopathy, 1 patient with myoclonus epilepsy with ragged-red fibers (MERRF), 6 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 5 patients with undefined mitochondrial encephalomyopathy and 8 patients with mitochondrial myopathy. Cardiac involvement was evaluated by electrocardiogram (ECG), chest roentgenogram and echocardiogram. Abnormality of mt DNA was examined using Southern blotting and polymerase chain reaction method in 25 patients. Defects of the respiratory chain were examined in 27 patients. All of the KSS and probable KSS showed heart block, and 2 of the 3 patients showed abnormalities on echocardiogram. Five of the 15 patients with ocular myopathy showed abnormalities on EGG. Four of the 6 patients with MELAS showed abnormalities on ECG, 1 showed cardiomegaly, and 3 showed left ventricular hypertrophy on echocardiogram. Three of the 5 patients with undefined mitochondrial encephalomyopathy showed abnormalities on ECG, 2 showed cardiomegaly and 2 showed asymmetric septal hypertrophy and wall motion abnormalities on echocardiogram. Large-scale deletions of mt DNA were detected in all of the KSS and probable KSS, and 7 patients with ocular myopathy. Deletions of mt DNA in the skeletal and cardiac muscles were proved to be identical in a case of KSS. A point mutation in mt DNA was detected in 5 patients with MELAS. Defects of the respiratory chain were detected in 22 patients. In conclusion, cardiac involvement is frequently seen in mitochondrial disease. Abnormality of ECG, especially heart block, is characteristic of KSS. Left ventricular hypertrophy is characteristic of mitochondrial encephalomyopathy.